Outpatient Antipsychotic Use and Severe COVID-19: Avoiding the Impact of Age in a Real-World Data Study.

BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). CONCLUSIONS: The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.

Dentists' knowledge, attitudes and perceptions of antibiotic prescribing: A systematic review.

OBJECTIVE: This study aims to explore dentists' knowledge, attitudes, and perceptions regarding antibiotic use. METHODS: We conducted a systematic review of dentists' knowledge, attitudes and perceptions regarding antibiotic use, by searching the MEDLINE, EMBASE and Web of Science for all original paper published from January 1990 to July 2023, in accordance with the Preferred Reporting Items for systematic Reviews and Meta-analyses (PRISMA 2020) guidelines. RESULTS: The review included 37 papers, (7 qualitative and 30 quantitative studies). Modifiable factors (knowledge, attitudes) were reported as being associated with antibiotic prescribing by dentists which were cited in 30 of the 37. These attitudes most frequently identified by dentists were: complacency (22/29); lack of trust (16/29); the need to postpone the dental procedure (17/29); and fear (8/29). Gaps in knowledge were also identified (15/29). Only one of the included articles quantified the influence between the reported modifiable factors and antibiotic prescribing. CONCLUSIONS: The review emphasizes that dentists' antibiotic prescribing is predominantly influenced by modifiable factors. This insight informs the potential for targeted interventions to curtail inappropriate antibiotic use, contributing to global efforts in reducing antibiotic resistance. The protocol of this systematic review can be found in PROSPERO under registration no. CRD42021253937.

Comparing AGS Beers 2019, STOPP version 2, and EU(7)-PIM list in Portuguese older adults in primary health care.

PURPOSE: This study aims to identify PIM prevalence in older adults according to the 2019 Beers criteria, Screening Tool of Older Person's Prescriptions version 2 (STOPP v2) criteria, and the Portuguese EU(7)-PIM list and also to analyze the concordance between these criteria. METHODS: A retrospective study was conducted among 1200 Portuguese older adults (≥ 65 years old), users of primary health care. Demographic, clinical, and pharmacological data were collected concerning the period between April 2021 and August 2022. A comparative analysis was performed between the three PIM identification criteria, and the concordance was determined according to the Lin concordance correlation coefficient. RESULTS: The mean age was 76.3 (SD 7.7) years old and 57.6% of the older adults were females. Our findings indicate varying prevalence rates among these criteria with 63.8% (95% CI 61.0-66.6%), 66.8% (95% CI 64.1-69.5%), and 50.1% (95% CI 47.2-53.0%) of the older adults take at least one PIM according to the EU(7)-PIM list, Beers 2019, and STOPP v2 criteria, respectively. The highest prevalence observed was for proton pump inhibitors according to EU(7)-PIM list (30.1%, 95% CI 27.6-32.9) and Beers criteria (30.1%, 95% CI 27.6-32.9) and alprazolam according to STOPP v2 criteria (10.1%, 95% CI 8.4-11.9%). A poor concordance between criteria was observed (< 0.834). The highest concordance coefficient was found between the EU(7)-PIM list and the Beers criteria (0.833), and the lowest between the EU(7)-PIM list and STOPP criteria (0.735). CONCLUSION: This study reveals varying prevalence rates of PIM in older adults, as assessed by different criteria, and highlights the need for targeted interventions and improved prescribing practices. In the future, studies should focus on the occurrence of negative outcomes in older adults associated with PIM consumption.

What determines health professionals' COVID-19 vaccine hesitancy? A nationwide study.

INTRODUCTION: To contain the COVID-19 pandemic, higher vaccination rates are essential. However, as vaccine hesitancy is a reality, it is important to understand what drives health professionals to refuse getting vaccinated against COVID-19, who have been in the frontline of this pandemic since its beginning and may be key actors to improve vaccine coverage among their patients. PURPOSE: This study aims to assess the factors associated with vaccine hesitancy (VH) among health professionals (physicians, nurses, pharmacists and dentists). METHODS: A nationwide cross-sectional study was conducted through an online survey, with 890 Portuguese health professionals. A logistic regression analysis was used to determine the adjusted odds ratio (OR) of the independent variables (perceptions, knowledge and attitudes) per 1-point increase in the Likert scale and VH. RESULTS: Complacency, communications, confidence and convenience were strongly associated with VH probability. Concerns about vaccines' efficacy (ORPhysicians  = 8.33, 95% CI: 4.51-15.36) and safety (ORNurses  = 11.07, 95% CI: 4.12-29.77) increase the risk of VH on all health professional groups. A reduction of VH probability is associated with higher risk perceptions of getting infected (1/ORNurses  = 2.76, 95% CI: 1.52-5.02) and suffering complications (1/ORNurses  = 33.72, 95% CI: 8.48-134.13), higher confidence in the effectiveness of COVID-19 vaccines (1/ORDentists  = 12.29, 95% CI: 2.91-51.89), risk perception of getting infected if vaccinated (1/ORPhysicians  = 14.92, 95% CI: 6.85-32.50), risk of suffering from complications after getting vaccinated, and higher trust levels on the information transmitted by competent authorities (1/ORDentists  = 17.76, 95% CI: 3.83-82.22). CONCLUSIONS: To reduce COVID-19 VH, which appears to be highly influenced by perceptions, knowledge and attitudes, it is essential to promote interventions directed to transforming these potentially modifiable determinants.

Perceptions, knowledge and attitudes about COVID-19 vaccine hesitancy in older Portuguese adults.

BACKGROUND: Coronavirus 2019 (COVID-19) has become a public-health emergency of international concern. Most efforts to contain the spread and transmission of the virus rely on campaigns and interventions targeted to reduce Vaccine Hesitancy and Refusal (VHR). OBJECTIVE: this study aims to assess the major factors associated with VHR in the older population in Portugal. METHODS: a nation-wide cross-sectional study was conducted in the older Portuguese population (≥65 years old) through computer-assisted telephone interviewing. Logistic regression was used to determine the adjusted odds ratio (OR) of the independent variables (perceptions, knowledge and attitudes) and of the outcome (VHR). RESULTS: the response rate was 60.1% (602/1,001). Perceptions, knowledge and attitudes were strongly associated with VHR probability. A 1-point Likert scale increase in concerns about the vaccines' efficacy and safety increased the risk of VHR by 1.96 (95% confidence interval [CI]: 1.40-6.28) and 3.13 (95%CI: 2.08-8.22), respectively. A reduction of VHR probability for 'reliability of the information released by social media' (OR = 0.34, 95%CI: 0.16-0.70) and for 'trust in national and international competent authorities' (OR = 0.34, 95%CI: 0.17-0.69) is also observed per 1-point increase. CONCLUSIONS: as VHR seems to be strongly associated with perceptions, knowledge and attitudes, the design and promotion of vaccination campaigns/educational interventions specifically targeted at changing these potentially modifiable determinants may help to tackle COVID-19 VHR and achieve a wider vaccine coverage.

Nuclear Envelope Alterations in Myotonic Dystrophy Type 1 Patient-Derived Fibroblasts.

Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease characterized by myotonia, progressive distal muscle weakness and atrophy. The molecular mechanisms underlying this disease are still poorly characterized, although there are some hypotheses that envisage to explain the multisystemic features observed in DM1. An emergent hypothesis is that nuclear envelope (NE) dysfunction may contribute to muscular dystrophies, particularly to DM1. Therefore, the main objective of the present study was to evaluate the nuclear profile of DM1 patient-derived and control fibroblasts and to determine the protein levels and subcellular distribution of relevant NE proteins in these cell lines. Our results demonstrated that DM1 patient-derived fibroblasts exhibited altered intracellular protein levels of lamin A/C, LAP1, SUN1, nesprin-1 and nesprin-2 when compared with the control fibroblasts. In addition, the results showed an altered location of these NE proteins accompanied by the presence of nuclear deformations (blebs, lobes and/or invaginations) and an increased number of nuclear inclusions. Regarding the nuclear profile, DM1 patient-derived fibroblasts had a larger nuclear area and a higher number of deformed nuclei and micronuclei than control-derived fibroblasts. These results reinforce the evidence that NE dysfunction is a highly relevant pathological characteristic observed in DM1.

Potentially Inappropriate Medication Prescribing in Older Adults According to EU(7)-Potentially Inappropriate Medication List: A Nationwide Study in Portugal.

Background: Portugal has among the highest rates of dependency among older adults in Europe. Older adults with aging-related comorbidities are prone to the use of potentially inappropriate medication (PIM). Objective: The aim of this study was to analyze PIM prescriptions in older Portuguese adults, as well as the change rate of PIM prescriptions over time, and assess the geographical variability between the different regions of mainland Portugal. Methods: Using a national database, PIM prescriptions were analyzed for older adults (aged 65 years and older) between 2019 and 2021 from 2 perspectives: PIM-defined daily dose (DDD) frequency (%) and DDD per 1000 inhabitants per day (DID). Results: Overall, mainland Portugal presented a PIM DDD frequency of 9.20%, which was relatively higher in Alentejo and Centro and lower in the North. Alprazolam, fluoxetine, and rivaroxaban were PIM with higher DDD frequency values. Over the years, the DID change rates for these three PIM were -3.80%, -14.86%, and +18.54%, respectively, depending on the geographic region. Alprazolam and fluoxetine were mostly prescribed to older women, whereas rivaroxaban was mostly prescribed to older men. Conclusions: These results emphasize the need to implement initiatives and interventions to decrease PIM prescriptions in older adults.

Health professionals perception and beliefs about drug- related problems on polymedicated older adults- a focus group study.

BACKGROUND: Polymedicated older patients are at greater risk of suffering from adverse events. For this reason, the detection of both inappropriate polypharmacy and polypharmacy-associated Drug-Related Problems (DRPs) are essential to improve the health and wellbeing of older adults and to reduce healthcare costs. This work aims to explore health professionals' perceptions and opinions about polypharmacy and the handling of medicines by polymedicated older adults. METHODS: Thirteen focus groups with 94 health professionals (20 community pharmacists, 40 general practitioners and, 34 nurses) were conducted in primary healthcare centers of the center region of Portugal. Participants were asked to discuss their perceptions and beliefs concerning DRPs in polymedicated older adults. The sessions were audiotaped. After the transcription and coding of focus group sessions, a thematic analysis was done. RESULTS: The following four main themes emerged from the 13 focus group sessions: poor compliance and polypharmacy- A perpetuated vicious cycle, organization of the healthcare system, interaction and communication between the health professionals, and strategies to prevent inappropriate polypharmacy. CONCLUSIONS: The lack of both an efficient network of information and Interaction and communication between Health professionals makes the detection and/ or prevention of polypharmacy in older adults difficult. The implementation of new models to manage and/or prevent polypharmacy based on health professional perception and beliefs is essential to prevent DRPs and improve compliance among older adults.

A Mobile App to Support Clinical Diagnosis of Upper Respiratory Problems (eHealthResp): Co-Design Approach.

BACKGROUND: The misuse of antibiotics is a global public health issue that fosters bacterial resistance and jeopardizes generational health. The development of validated tools such as web-based courses and mobile apps to enhance clinical decisions in upper respiratory infections is of great importance in reducing the incorrect use of antibiotics in these situations. OBJECTIVE: The aim of this study was to design and prevalidate the interface of a mobile app to assist and provide clinical support in the diagnosis of upper respiratory problems. We aimed to assess the adequacy and usability of the interface of the tool in the belief that it could be beneficial to health care delivery in the clinical decision setting. METHODS: Using a co-design approach that brought together professionals in interface design and experts in pharmacology and pharmacoepidemiology, the mobile app interface was evaluated through peer review sessions held by interface design professionals on a heuristic survey. The reviewers accessed a high-fidelity interactive mock-up of the interface and filled in a questionnaire to assess the dimensions of layout and visual design and navigation and tasks. The resulting feedback of this evaluation supported the redesign of the primary interface, which was assessed for the second time by 2 of the previously mentioned reviewers. RESULTS: With 4 as the highest score, the interface scored a mean of 3.16 (SD 0.45; median of the means 3.2) for layout and visual design and a mean of 3.43 (SD 0.33; median of the means 3.51) for navigation and tasks, reflecting an overall positive evaluation. The open-ended commentaries allowed us to better understand specific recommendations of the reviewers. Throughout this section, approximately 0.98 comments per parameter were registered, reflecting a high level of effectiveness of the chosen parameters in identifying potential problems. The resultant beta version of the interface, addressing the majority of the detected problems, was further assessed by 2 of the previous reviewers, validating the new design. Future tests with physicians and pharmacists will help assess credibility and user experience dimensions. CONCLUSIONS: Our study revealed that the designed interface is easy to interpret and use. Peer reviewers raised important issues that could be easily fixed and positively reassessed. As a result, the study enabled us to produce a new tool for interface usability assessment and a set of recommendations for developing mobile interfaces for clinical decision support systems in the scope of upper respiratory problems.

Effectiveness of an intervention to improve antibiotic-prescribing behaviour in primary care: a controlled, interrupted time-series study.

BACKGROUND: High rates of antibiotic misprescribing in primary care, with alarming clinical and economic consequences, highlight the urgent need for interventions to improve antibiotic prescribing in this setting. OBJECTIVES: To assess the effectiveness on antibiotic prescribing quality indicators of a multifaceted intervention targeting health professionals' and patients' behaviour regarding antibiotic use. METHODS: We conducted a pragmatic cluster-randomized controlled trial in the catchment area covered by Portugal's Central Regional Health Administration. The intervention consisted of a multidisciplinary, multifaceted programme involving physicians, pharmacists and patients, and comprising outreach visits for physicians and pharmacists, and educational materials for health professionals and patients. The following were assessed: relative ratios of prescription of penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins and fluoroquinolones; and the ratio of broad- to narrow-spectrum antibiotics. An interrupted time-series analysis for multiple-group comparisons was performed. The study protocol was registered on Clinical.trials.gov (NCT02173509). RESULTS: The participation rate in the educational intervention was 64% (197/309 GPs) in a total of 25 counties. Statistically significant improvements were obtained, not only in the relative prescription of penicillins sensitive to ß-lactamase (overall relative change of +896%) and penicillin combinations including ß-lactamase inhibitors (-161%), but also in the ratio of broad- to narrow-spectrum antibiotics (-200%). Statistically significant results were also obtained for third- and fourth-generation cephalosporins, though only in the immediate term. CONCLUSIONS: This study showed that quality indicators of antibiotic prescribing can be improved by tackling influences on behaviour including knowledge and attitudes surrounding physicians' clinical practice. Accordingly, these determinants must be considered when implementing interventions aimed at improving antibiotic prescribing.

Primary versus secondary source of data in observational studies and heterogeneity in meta-analyses of drug effects: a survey of major medical journals.

BACKGROUND: The data from individual observational studies included in meta-analyses of drug effects are collected either from ad hoc methods (i.e. "primary data") or databases that were established for non-research purposes (i.e. "secondary data"). The use of secondary sources may be prone to measurement bias and confounding due to over-the-counter and out-of-pocket drug consumption, or non-adherence to treatment. In fact, it has been noted that failing to consider the origin of the data as a potential cause of heterogeneity may change the conclusions of a meta-analysis. We aimed to assess to what extent the origin of data is explored as a source of heterogeneity in meta-analyses of observational studies. METHODS: We searched for meta-analyses of drugs effects published between 2012 and 2018 in general and internal medicine journals with an impact factor > 15. We evaluated, when reported, the type of data source (primary vs secondary) used in the individual observational studies included in each meta-analysis, and the exposure- and outcome-related variables included in sensitivity, subgroup or meta-regression analyses. RESULTS: We found 217 articles, 23 of which fulfilled our eligibility criteria. Eight meta-analyses (8/23, 34.8%) reported the source of data. Three meta-analyses (3/23, 13.0%) included the method of outcome assessment as a variable in the analysis of heterogeneity, and only one compared and discussed the results considering the different sources of data (primary vs secondary). CONCLUSIONS: In meta-analyses of drug effects published in seven high impact general medicine journals, the origin of the data, either primary or secondary, is underexplored as a source of heterogeneity.

Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians.

OBJECTIVES: The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). METHODS: The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test-retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known-groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). RESULTS: Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. CONCLUSION: The final 11 item KAAR questionnaire appears to be valid, reliable and responsive.

Physicians' attitudes and knowledge concerning antibiotic prescription and resistance: questionnaire development and reliability.

BACKGROUND: Understanding physicians' antibiotic-prescribing behaviour is fundamental when it comes to improving antibiotic use and tackling the growing rates of antimicrobial resistance. The aim of the study was to develop and validate--in terms of face validity, content validity and reliability--an instrument designed to assess the attitudes and knowledge underlying physician antibiotic prescribing. METHODS: The questionnaire development and validation process comprised two different steps, namely: (1) content and face validation, which included a literature review and validation both by physicians and by Portuguese language and clinical psychology experts; and (2) reliability analysis, using the test-retest method, to assess the questionnaire's internal consistency (Cronbach's alpha) and reproducibility (intraclass correlation coefficient--ICC). The questionnaire includes 17 items assessing attitudes and knowledge about antibiotic prescribing and resistances and 9 items evaluating the importance of different sources of knowledge. The study was conducted in the catchment area covered by Portugal's Northern Regional Health Administration and used a convenience sample of 61 primary-care and 50 hospital-care physicians. RESULTS: Response rate was 64% (49% to retest) for primary-care physicians and 66% (60% to retest) for hospital-care physicians. Content validity resulted in 9 changes to professional concepts. Face validity assessment resulted in 19 changes to linguistic and interpretative terms. In the case of the reliability analysis, the ICC values indicated a minimum of fair to good reproducibility (ICC > 0.4), and the Cronbach alpha values were satisfactory (α > 0.70). CONCLUSIONS: The questionnaire developed is valid--in terms of face validity, content validity and reliability--for assessing physicians' attitudes to and knowledge of antibiotic prescribing and resistance, in both hospital and primary-care settings, and could be a very useful tool for characterising physicians' antibiotic-prescribing behaviour.

Nurses' attitudes and spontaneous adverse drug reaction reporting: a case-control study in Portugal.

AIM: To identify the attitudes and knowledge associated with adverse drug reactions (ADR) under-reporting by nurses. BACKGROUND: The voluntary reporting system is fundamental for expediting the detection of ADR during post-marketing surveillance. METHODS: We performed a case-control study. A self-administered questionnaire was sent by mail to 1325 nurses. The knowledge and attitudes related to ADR under-reporting were primarily based on Inman's seven deadly sins. RESULTS: The overall response rate was 34.2%. Nurses working in primary care were 12-fold more likely to report an ADR. A change of attitude increased the probability of ADR reporting for:'The belief that the one case an individual nurse might see could not contribute to medical knowledge'; 'I do not know how the information reported is used by the system'; 'I would be more likely to report if the method was easier'; 'I think the most correct way to report is to inform the doctor' and 'I do not have time to think about the involvement of the drug in ADRs'. CONCLUSIONS: Our study shows that the beliefs of nurses, such as 'one single report would not make any difference' and 'the pharmacovigilance system is very complex', act as a barrier to ADR reporting. IMPLICATIONS FOR NURSING MANAGEMENT: It is important to clarify the ADR reporting procedure and increase the nurses reporting rate.

Use of off-label and unlicenced drugs in hospitalised paediatric patients: a systematic review.

PURPOSE: The aim of this review is to assess the extent of the use of off-label and/or unlicenced drugs among hospitalised children. METHODS: A systematic search was made in MEDLINE-PubMED for papers published from 1994 to 2012, addressing the prescription of off-label and/or unlicenced drugs for the paediatric population in hospital care. RESULTS: Of the 829 studies retrieved, 34 met the inclusion criteria. Prescriptions ranged from 12.2 to 70.6 % for off-label and from 0.2 to 47.9 % for unlicensed drugs. The percentage of children who received at least one off-label and/or unlicensed drug ranged from 42.0 to 100 %, with newborns being the population that received most of such drugs. Off-label prescriptions were essential for dose modification (7.1-73.1 %) and unlicensed prescriptions for formulation modification purposes (3.6-100 %). CONCLUSIONS: These findings show that: (i) off-label and/or an unlicensed prescribing is widespread among the hospitalised paediatric population worldwide, (ii) there is no consensus on a definition of off-label and/or unlicensed drugs and (iii) preterm newborns receive most off-label and/or unlicensed drugs. By shedding new light on off-label and/or unlicensed drug prescribing, these findings will hopefully contribute to generating new, more effective knowledge about the paediatric population's need for quality drugs that are both safe and efficacious.

Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems.

Antidepressants have been associated with a low incidence of idiosyncratic hepatic injury. Some of them, nefazodone or amineptine, were observed to induce severe hepatic injury and withdrawn from the market. Recently, some cases of this severe condition have been reported in association with agomelatine use. Therefore, the objective of this study is to learn the risk of hepatic damage with agomelatine as compared with other new antidepressants. We took data from the Spanish, French, Italian, and Portuguese pharmacovigilance system databases. A case/noncase approach to assess the strength of the association between whichever antidepressant and hepatotoxicity was performed; cases were defined as reports of hepatotoxicity; noncases were reports of all reactions other than hepatotoxicity. Exposure was the recording of a new antidepressant in a report, whether or not it was suspected of causing the reaction. During the period surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants assessed. They represent 10.3% of all cases collected for these drugs; the corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of hepatotoxicity associated with agomelatine were collected since its introduction until the end of the period studied; they account for a percentage of 14.6. Agomelatine was statistically associated with hepatotoxicity in Spain [reporting odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4-9.7)], France (ROR, 2.4 [95% CI, 1.5-3.7]), and Italy (ROR, 5.1 [95% CI, 1.7-14.0]). Current results support the idea of agomelatine to be related to a higher hepatotoxicity risk. Physicians should consider early discontinuation if the condition is suspected; health authorities should promptly explore the best regulatory actions to be taken.

Educational interventions to improve prescription and dispensing of antibiotics: a systematic review.

BACKGROUND: Excessive and inappropriate antibiotic use contributes to growing antibiotic resistance, an important public-health problem. Strategies must be developed to improve antibiotic-prescribing. Our purpose is to review of educational programs aimed at improving antibiotic-prescribing by physicians and/or antibiotic-dispensing by pharmacists, in both primary-care and hospital settings. METHODS: We conducted a critical systematic search and review of the relevant literature on educational programs aimed at improving antibiotic prescribing and dispensing practice in primary-care and hospital settings, published in January 2001 through December 2011. RESULTS: We identified 78 studies for analysis, 47 in primary-care and 31 in hospital settings. The studies differed widely in design but mostly reported positive results. Outcomes measured in the reviewed studies were adherence to guidelines, total of antibiotics prescribed, or both, attitudes and behavior related to antibiotic prescribing and quality of pharmacy practice related to antibiotics. Twenty-nine studies (62%) in primary care and twenty-four (78%) in hospital setting reported positive results for all measured outcomes; fourteen studies (30%) in primary care and six (20%) in hospital setting reported positive results for some outcomes and results that were not statistically influenced by the intervention for others; only four studies in primary care and one study in hospital setting failed to report significant post-intervention improvements for all outcomes. Improvement in adherence to guidelines and decrease of total of antibiotics prescribed, after educational interventions, were observed, respectively, in 46% and 41% of all the reviewed studies. Changes in behaviour related to antibiotic-prescribing and improvement in quality of pharmacy practice was observed, respectively, in four studies and one study respectively. CONCLUSION: The results show that antibiotic use could be improved by educational interventions, being mostly used multifaceted interventions.

Magnitude and Determinants of Long-term Use of Proton Pump Inhibitors Among Portuguese Older Adults in Primary Health Care.

PURPOSE: Proton Pump Inhibitors (PPIs) have been associated with several adverse effects of particular concern in older populations. Their use for a period longer than 8 weeks is not recommended for older adults. Strategies to discontinue PPIs have been offered; however, their use remains high. This study aims to characterize PPI use in Portuguese older people and to identify the factors associated with potentially inappropriate use. METHODS: A cross-sectional study was conducted on 1200 randomly selected older adults (≥65 years of age), users of primary health care facilities in the Regional Health Administration (Administração Regional de Saúde of Centro [ARSC]) of Portugal between April 2021 and August 2022. Data concerning their characteristics and PPI use were provided by the Shared Services of the Health Ministry (Serviços Partilhados do Ministério da Saúde) and collected retrospectively. Associations between independent variables and PPI use were investigated by logistic regression analysis. FINDINGS: Of the older adults, 37.92% were receiving PPIs and 78.68% of them were taking them for a longer period than recommended; 49.79% were taking PPIs without having any digestive system-related disease. Multivariate analysis showed that the prolonged use of PPIs was not associated with any specific pattern, although inappropriate PPI use is high among Portuguese older adults. IMPLICATIONS: Long-term PPI use in older adults is widespread and does not fit any particular patient profile; therefore, cross-cutting educational interventions should be designed independently of the patient's pathologic condition or treatment.

Barriers and facilitators of health professionals in adopting digital health-related tools for medication appropriateness: A systematic review.

Objective: Digital health is described as the use and development of all types of digital technologies to improve health outcomes. It could be used to prevent medication errors, a priority for health systems worldwide. However, the adoption of such tools remains slow. This study aims to identify factors (attitudes, knowledge and beliefs) acting as barriers and/or facilitators reported by healthcare professionals (HCPs) for the adoption of digital health-related tools for medication appropriateness. Methods: A systematic review was performed by searching the literature in the MEDLINE PubMed, and EMBASE scientific databases for original articles regarding qualitative and quantitative data. Results: Fifteen articles were included and a total of 125 barriers and 108 facilitators were identified, consolidated and categorized into technical (n = 48), organizational (n = 12), economical (n = 4), user-related (n = 34), and patient-related (n = 8) components. The most often reported barriers and facilitators were technical component-related ones concerning the need for additional training (n = 6), the time consumed (n = 6), and the easy way of using or learning how to use the tools (n = 9), respectively. Regarding setting analysis, agreement with clinical decision recommendations and impact on the doctor-patient relationship were more valued in primary care, while the user interface and system design were in the hospital. Conclusions: The barriers and facilitators identified in this study provide relevant information to developers and it can be used as a starting point for the designing of successful digital health-related tools, specifically related to medication appropriateness. Future research includes economic evaluation-focused studies and in-depth case studies of specific barriers and facilitators.

Medicines for an aging population: The EMA perspective and policies.

The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered. Possible concrete actions are presented to improve the design of clinical trials, the data collection both pre- and post-approval, the assessment of the findings, and the communication to assist informed prescription and safe medicine taking. Implementation and prioritization of these actions should be done from the perspective of addressing the needs of patients while maximizing efficient use of resources, with the aim of integrating geriatric aspects into routine medicines development and assessment.